Objective: To describe cortical and subcortical 18F-AV-1451 binding in Parkinson’s disease patients with and without mild cognitive impairment (PD-MCI and PD-nonMCI).

Background: The radioligand 18F-AV-1451 binds tau protein, primarily in the form of paired helical filaments, which is present in increasing amounts in Alzheimer’s disease from pre-dementia stages until death. In varying degrees, 18F-AV-1451 also binds to pathological tau in Parkinson’s disease dementia and dementia with Lewy bodies; to straight tau filaments seen in progressive supranuclear palsy and corticobasal degeneration; and to neuromelanin-containing cells in the substantia nigra. We previously demonstrated decreased 18F-AV-1451 binding in the substantia nigra of patients with Parkinson’s disease, thought to reflect loss of neuromelanin-containing dopaminergic neurons.

Methods: Twenty-six Parkinson’s disease patients and 24 healthy age-matched controls had 18F-AV-1451 positron emission tomography (PET) and most Parkinson’s disease patients also had dopamine transporter imaging, using 123I-FP-CIT. Neuropsychological evaluation as recommended by Litvan et al. was performed to detect the presence of PD-MCI. Voxel-wise comparisons between groups were conducted using SPM12. Regional analysis of 18F-AV-1451 PET was performed using PMOD, and regional analysis of dopamine transporter imaging was performed using Hermes BRASS.

Results: Nine Parkinson’s disease patients were identified as PD-MCI and 17 as PD-nonMCI. Using 18F-AV-1451, no significant differences between groups were found in cortical areas. In the substantia nigra, PD-nonMCI patients displayed significantly lower 18F-AV-1451 signal than healthy controls, and PD-MCI patients had even lower signal than PD-nonMCI. No differences were found in other sub-cortical areas using 18F-AV-1451. Voxel-wise analysis of 18F-AV-1451 PET uptake failed to reveal any differences surviving family-wise error correction. Comparing PD-MCI and PD-nonMCI using dopamine transporter imaging, PD-MCI patients were found to have a significant decrease of presynaptic dopamine transporter density in the combined striatae.

Conclusions: Our results indicate that cortical binding of the tau radioligand 18F-AV-1451 is rare in pre-dementia Parkinson’s disease. However, lower 18F-AV-1451 signal of the substantia nigra likely reflects progression of nigrostriatal dysfunction in PD-MCI compared to PD-nonMCI.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/18f-av-1451-pet-imaging-in-pre-dementia-parkinsons-disease/